Lecture 3 Flashcards
why do we need blood vessels
o2 transport, heart regulation, compartmentalising blood, recruitment of immune cells to target sites, nutrient and waste transport and thermal adaptation
what affects blood vessels
O2 and CO2 conc, lipids, lipoproteins and atherosclerosis, glucose, insulin and diabetes, solid tumours, free radicals, platelets and leukocytes and almost all hormones
what causes vasoconstriction
increase in O2, decrease in CO2, cold
what cause vasodilation
decrease O2, increase CO2, increase NO2
what 3 small molecules secreted by endothelial cells act on smooth muscle to control vasodilation
PGI2 No and EDFH
how is NO synthesised
eNOS catalyses the section of 2 molecules of arginine + 2NADPH and 2O2 to form citulline, 2NADP, 2H2O and NO
how is eNOS stimulated
ligands of G protein coupled receptors such as ach receptors activate PLC and the release of Ca2+. caM binds Ca2+ forming a cofactor for eNOS. alternatively sheer forces, VEGF and other hormones can cause activation
describe the eNOS signalling pathway and how it leads to vasodilation
eNOS binds guanylyl cyclase and induces cyclic GMP production which activates protein kinase G which modulates a number of proteins which induce muscle relaxation including activating myosin light chain phosphatase, inhibiting myosin light chain kinase and promoting calcium reputake by the ER
how is eNOS signalling terminated
hydrolysis of cGMP by phsphodiesterase
why does NO target and inhibit the protein which is responsible for the secretion of WPBs
because WPBs contain VWF which regulates coagulation by forming tightly packed filaments and can cause platelet activation and thrombi to grow resulting in blood clots. therefore NO is anti-thrombogenic
how does PGI2 control vasodilation
a stimulus which increases CA2+ which activates the MAPK pathway, activating phospholipase A2. this then moves to membranes and cleaves phospholipids in the membrane releasing arachidonic acid and lysopjopholipid. AA is processed by COX1 and 2 to form prostaglandins which are converted to prostacyclin (PGI2) by PGI synthase. these diffuse from epithelial ells to IP receptors on smooth muscle cell which activates adenylate cyclase to for cAMP which causes vasodilation by excluding calcium from the cell
how does EDHF control vasodilation
this process is not well understood but thought to be involved in vasodilation of smaller diameter blood vessels
how does atherosclerosis occur
a plaque in the artery reduces the diameter of the lumen. the endothelium becomes sticky and expresses a number of adhesion molecules which attract monocytes. these migrate into the intima and phagocytose oxidised lipids causing them to transform into foam cells. foam cells release cytokines causing accumulation of cells such as smooth muscle and fibroblasts in the intima. the intima thickens and grows in towards the lumen, compromising blood flow. this causes necrosis and apoptosis which causes breakage of the endothelium. proteins which belong to lower layers are expressed to the blood stream which activates coagulation and the platelet cascade. this forms a thrombus which further occludes the lumen or even detach and get stuck in a smaller blood vessel blocking it completely leading to myocardial infarction or stroke.
how do platelets form a thrombus
both the intrinsic and extrinsic pathway activate factor X which turns prothrombin into thrombin which converts fibrinogen to fibrin which binds to platelets and forms a blood clot
why is it harder for activated platelets to pass through the blood stream
they change shapes from flat discs to have projections as a result of activation of Rho GTPases
